| Summary: | <p>Viral vectors are a next-generation vaccine platform that elicit a robust response from the humoral and cellular arms of the immune system. The importance of this vaccine platform was demonstrated during this PhD with the emergence of SARS-CoV-2 and the development of the chimpanzee adenovirus-vectored vaccine ChAdOx1 nCoV-19. Although this vaccine is immunogenic, pre-existing infections such as cytomegalovirus have been shown to reduce antigen-specific vaccine immunogenicity in other vaccines. Cytomegalovirus is a chronic herpesvirus that is prevalent in ~40-100% adults worldwide, and although infection is often asymptomatic it can increase the frequency of terminally differentiated immune cells in healthy young adults.</p>
<p>This thesis aims to characterise the effect of viral vectored vaccines including ChAdOx1 on immune populations not traditionally studied in vaccinology, including NK cells. It also investigates how cytomegalovirus impacts the immune phenotype and vaccine immunogenicity in humans and mice. This thesis demonstrates that viral vector vaccination activates NK cells and induces robust cytokine secretion in both mouse and human studies, although can affect NK cell phenotype following vaccination with MVA. Furthermore, CMV seropositivity elicits a terminally differentiated phenotype on the immune system, but does not affect viral vector vaccine immunogenicity following a single dose or homologous boost of ChAdOx1. Overall, these findings which are especially important for the ongoing vaccination regimen against SARS-CoV-2, and provide further insight into the interplay of viral vectored vaccines and viral infection on the immune system.</p>
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